Background Percutaneous cryoablation (PCA) is an increasingly utilized treatment for stage I renal cell carcinoma (RCC), albeit without supportive level I evidence. Purpose Primary objective was to determine the 10-year oncologic outcomes of PCA for stage I RCC in a prospective manner. Secondary objectives were to compare outcomes after partial nephrectomy (PN) and radical nephrectomy (RN) from the National Cancer Database (NCDB), to determine long-term renal function, and to determine the risk of metachronous disease. Materials and Methods In this institutional review board-approved prospective observational study (2006-2013), study participants with single, sporadic, biopsy-proven RCC were included to calculate the 10-year overall survival, recurrence-free survival, and disease-specific survival after PCA. Results were compared with matched PN and RN NCDB cohorts. Overall and recurrence-free survival probabilities were estimated by using nonparametric maximum likelihood estimator. Disease-specific survival was estimated by using the redistribution-to-right method. Age at diagnosis was stratified as a risk for survival. The effect on estimated glomerular filtration rate, serum creatinine level, and the risk for hemodialysis and metachronous disease were calculated. Results One hundred thirty-four patients (46% men) with single, sporadic, biopsy-proven RCC (median size ± standard deviation, 2.8 cm ± 1.4) were included. Overall survival was 86% (95% confidence interval [CI]: 80%, 93%) and 72% (95% CI: 62%, 83%), recurrence-free survival was 85% (95% CI: 79%, 91%) and 69% (95% CI: 59%, 79%) (improved over surgery), and disease-specific survival was 94% (95% CI: 90%, 98%) at both 5 years and 10 years (similar to surgery), respectively. The 10-year risk of hemodialysis was 2.3%. Risk of metachronous RCC was 6%. Charlson/Deyo Combined Comorbidity score analysis showed decreasing overall survival with increasing comorbidity index. The PCA cohort outperformed both RN- and PN-matched subgroups in all Charlson/Deyo Combined Comorbidity score categories. Conclusion Percutaneous cryoablation yielded a 10-year disease-specific survival of 94%, equivalent to that reported after radical or partial nephrectomy. Overall survival probability after percutaneous cryoablation at 5 years and 10 years was longer than for radical or partial nephrectomy, especially for patients at higher risk (Charlson/Deyo Combined Comorbidity score ≥2). © RSNA, 2020.